Langerhans/dendritic cells (DC) appear to be critical in the establishment of mucosally acquired HIV infection. Primary HIV infection is largely initiated by macrophage tropic (M-tropic) viruses which use the beta-chemokine receptor CCR5, in addition to CD4, for entry. This occurs despite concommitant exposure to T-cell tropic (T-tropic) viruses which use the alpha-chemokine receptor CXCR4 in addition to CD4 for entry. The mechanisms of this restriction are unknown. Individuals homozygous for a 32 base-pair deletion in CCR5 (delta32CCR5) lack surface expression of CCR5 and are with rare exception protected from HIV infection although they have normal CXCR4 expression and their cells are infectable with T-tropic viruses in vitro. The purpose of these studies is to evaluate these delta32CCR5 homozygous individuals to determine whether DC contribute to the M-tropic restriction of primary infection. We pulsed DC from wild-type (normal CCR5 genotype, WT) and delta32CCR5 individuals with limiting dilutions of HIV strains of different tropisms and co-cultured them with autologous or allogeneic CD4+ T cells; culture supernatants were monitored for productive infection by RT assay. We also stimulated CD4+ T cells with PHA and infected them with limiting dilutions of the same HIV strains, monitoring for infection by RT assay. We found that T-tropic, but not M-tropic viruses enter delta32CCR5 DC, whereas both types of viruses efficiently enter WT DC. However, despite the lack of viral entry, DC from delta32CCR5 individuals are capable of transfering M-tropic virus to WT CD4+ T cells. This is found even when CD4+ T cells are added to DC up to 72 hours after pulsing with HIV. The time required for DC to migrate from the mucosa to draining lymph nodes is approximately 24-48 hours. Thus, the block to infection with M-tropic viruses in delta32CCR5 individuals would seem to be at the level of the CD4+ T-cell, not the DC. T-tropic HIV strains are passed from both WT and delta32CCR5 DC to autologous or allogeneic CD4+ T cells with similar efficiencies. Thus, DC and CD4+ T cells, in this system of DC-CD4+ T-cell interaction, do not seem to be responsible for the protection from T-tropic viruses observed in vivo in delta32CCR5 homozygous individuals.